DESCRIPTION: (Investigator's abstract): Significance. Strabismus - misalignment of the visual axes - affects some 3% of the population and is a significant cause of visual disturbances such as diplopia, amblyopia, and stereoblindness. Whether the cause is central or orbital, definitive therapy for strabismus is usually surgical. Nevertheless, accuracy of surgical treatment remains disappointingly low: 20-50% of cases require multiple surgeries, each exposing patients to additional morbidity and expense. A validated computational model of ocular static mechanics would improve diagnosis and treatment planning, and yet has been elusive, due to absence of a concerted clinical-basic science collaboration devoted to its development. Such a model would also facilitate basic research on central or innervational causes of strabismus by allowing isolation of mechanical components of disease states, surgical manipulations, and healing processes. Aims and Methods. The "SQUINT" computational biomechanical model of binocular alignment is a system of equations describing static equilibrium of the globes and orbital tissues, implemented as a computer program. We propose to develop, test, and apply the SQUINT model. Development of the model will include (a) eliminating the existing assumptions regarding reciprocal innervation by implementing globe translation force-balance constraints, and (b) incorporating a novel treatment of the previously-neglected role of orbital connective tissues, suggested by our previous 3-dimensional magnetic resonance imaging (MRI) studies of functional relationships of extra-ocular muscle paths to the globe. We will seek further evidence for connective tissue "pulleys", with new MRI studies of patients with conditions in which muscles abnormally strain connective tissues: varieties of Duane's retraction syndrome, and muscle transposition surgery performed with different surgical techniques. These studies will permit non-invasive, quantitative determination of mechanical properties of previously-inaccessible connective tissues. We will develop and prospectively test the model using extensive pre- and post-operative Hess test binocular alignment data, saccadic trajectory measurements, intra-operative mechanical measurements, and MRI data, collected specifically for this purpose. We will apply the model to study the effects on alignment of post-surgical healing, using it in conjunction with longitudinal post-surgical data, to infer orbital and innervational changes.